Seminars

A new seminar cycle starts in September.

You can read details of the seminars if you click on each as well as you can find a concluding page under "Calendar".

Seminars can be booked individiually as well. If you wish to register individually to selected seminars you can find Registration links in each seminar description. If you like to apply to the Certificate programme, please go to applicaton.

Principles of registration and certification of medical devices and device/drug combinations

The subject area regulatory affairs ensures that the quality, safety and efficacy of the medicinal product is in line with legal requirements for the purpose of marketing safe and efficacious medicinal products solely in the interests of public health. Regulatory affairs is primarily a specialty of the pharmaceutical industry. The function encompasses all strategic, operational and administrative activities required to obtain official authorisation for Clinical Trials, marketing and distributing of medicinal products, post-marketing changes and obligations and manufacture and the activities related to pharmacovigilance. Seminar 1 provides the basis for all activities of a regulatory affairs professional since it imparts detailed knowledge on the pharmaceutical legislation, the regulatory institutions and stakeholders and their interaction and on the Modules 1 and 2 of the marketing authorisation dossier. Modules 3, 4 and 5 of the marketing authorisation dossier are dealt with in Seminar 4 of this course, specifically describing what is relevant for biopharmaceuticals. This seminar furthermore deals with the particulars of small and medium size enterprises and all regulations related to biopharmaceuticals. It also provides the legal details on orphan drug regulations and on the role and activities of the ICH process.

Approval in other regions - process and essentials of the relevant agencies

Seminar 2 provides in-depth knowledge on the procedures for marketing authorization applications, clinical trial authorisations and variations in the EU, USA, Japan and China. These regions are the most important markets for pharmaceutical products and the appropriate agencies such as the European national agencies, the EMA, the FDA and the Japanese MHLW have major influence on the regulatory strategy in pharmaceutical companies used to develop and submit new medicines. In order to authorise products in these markets successfully companies need to act according to the requirements and procedures of the different regions since they are not harmonised despite increasing efforts. For the EU the centralised procedure and the national mutual recognition and decentralised procedures are described in detail. Furthermore the documentation and steps required to obtain and maintain authorisations for clinical trials are discussed. During the life cycle of products their marketing authorization dossier is changed and the changes are subject to regulatory processes. For biopharmaceuticals these variations are frequently demanding in terms of data and dossier requirements. The seminar focuses in detail on product life cycle activities related to Europe but also provides an overview on the principles to be followed in other regions.

o Overview on the product class o Underlying immunology of the mode of action and clinical efficacy of vaccines o Current and new adjuvants o Manufacture and quality control requirements o Special characteristics of the pre-clinical and clinical development of vaccines o Pre- and post-authorisation documentation requirements for pandemic vaccines

Four unique product classes are introduced with respect to their regulation, the essential requirements for their development, their unique characteristics. Blood products stand for classical biologicals as they are manufactured from a biological source, i.e. human plasma. Their use is still required for many life-threatening and chronic diseases despite the progress recombinant technology made. Vaccines are mostly recombinant proteins and an increasing number of newly developed products is available which are all of special importance for the health systems. Both, blood products and vaccines, require special considerations in their manufacture, selection of starting material, testing and characterization and clinical development. The product class of monoclonal antibodies delivers an increasing number of novel medicines. Their development requires understanding of their special issues such as manufacturing technology options, species specificity for non-clinical development, pleiotropy, limitations of dose-finding approaches etc. Advanced therapy medicinal products are also unique as they are based on gene therapy, somatic cell or tissue engineering approaches. For these products the conventional requirements for biopharmaceuticals often do not apply as they are developed and manufactured for individual patients.

The development process of a biopharmaceutical has principle features in common with conventional drugs but is special in various aspects since their protein nature requires specific considerations. The four featured product classes illustrate how the current regulatory system ensures that a holistic approach of interaction between the manufacturing/testing, non-clinical and clinical team is followed during development.

Day 2

08.30 - 10.30 Vaccines: History of vaccine development and currently approved products // Vaccination impact and challenges for new developments // Underlying immunology of the mode of action and clinical efficacy of vaccines // Continuing evolution of vaccine antigens // The role of adjuvants in current and new vaccines // Special characteristics of clinical development of vaccines

13.30 – 15.30 Cervarix as an example for successful authorisation of a HPV vaccine: Introduction // Regulatory history // Clinical development - primary authorization and life cycle of the clinical indication // Success factors

Biopharmaceuticals are special since they stem from a biological source, or the protein structure is transcribed from genetic information and is expressed by a living cell. They are usually complex and large and the quality is determined by the manufacturing process, where consistency and stability need particular attention. This has implications on the way biopharmaceuticals are developed and regulated and particular guidelines are available which are covered in this seminar. The manufacturing process determines the quality of these products and the requirements for the key quality (CMC) issues are complex accordingly. Issues specific to biopharmaceuticals such as the manufacturing process definition, consistency, stability, definition of specifications, infectious agents' safety, comparability, bioassay are covered in this seminar as well as specific topics such as how changes of the process can impact the quality of these products. In addition to the European requirements on biopharmaceuticals the specific requirements of other global regions are dealt with in detail. Furthermore, the specific requirements for IMPs, investigational medicinal products are covered.

Understand the key quality (CMC) issues specific to biopharmaceuticals such as the manufacturing process definition, consistency, stability, definition of specifications, infectious agents' safety, comparability, bioassay use and apply them in the regulatory strategy

Understand and adapt the implications of the introduction of changes in the manufacturing process on the quality of the product, i.e. apply the comparability concept

Allows to conduct and steer the relevant regulatory strategy for CTA and MAA submissions for biopharmaceuticals due to knowing the rules and required data for Module 3

Understand the CMC essentials of an IMPD/CTA, CTD and MAA submission

Understand the regional differences in the scientific requirements for regulatory submissions for biopharmaceuticals and to utilize this in global submissions

Day 1

09.15 - 09.30 Welcome and introduction

09.30 - 10.30 The structure of the Quality Module 3 of the CTD for biopharmaceuticals and the relevant guidelinesThis session provides an introduction into Module 3 structure first which is used throughout the seminar as a kind of frame, in which the individual headings of the structure are embedded either as interactive sessions or as presentations.

10.30 - 11.00 Coffee break

11.00 - 11.30 First interactive session of the dossier and data requirements for the individual sections of the Module 3.

For all interactive sessions, Beatrix Metzner and Heike Volkmer develop with the audience the content related to biopharmaceuticals and will summarise at the end of the session the essentials.

15.00 – 15.45 Virus and TSE-safety of biopharmaceuticalsOverview on the risks of transmission of infectious agents // General principles of ensuring virus and TSE safety //  Principles of virus validation of the manufacturing process capacity to inactivate and remove viruses and TSE //  Requirements for early stage products (IMPs) versus late stage and commercial products (Phase 3 and MAA)

Biopharmaceuticals play an important role in the pharmaceutical industry since they deliver an increasing number of candidates for new product developments. They are however special and require certain considerations in their pre-clinical and clinical development. They are pleiotrop and immunogenic and their non-clinical pharmacodynamic and safety characterisation is often hampered by insufficiently relevant animal models. Biosimilars are developed following a special regulation and expanded programme as compared to conventional generics. This all has implications on the way biopharmaceuticals are developed and regulated. The particulars of the non-clinical and clinical requirements of biopharmaceuticals are covered and the specific considerations on the development of biosimilar medicinal products are part of this seminar as well. In this seminar case studies will also be presented on successfully authorized products, such as on a tri-functional monoclonal antibody and on a biosimilar. The seminar also introduces how to perform a benefit-risk assessment at the authorization stage and how to update it during life-cycle of the product.

Background of development and content of the Paediatric Regulation No 1901/2006 EC

The role of the EMA and of the Paediatric Committee (PDCO)

The Paediatric Investigational Plan (PIP) (Scope, legal aspects, considerations for developing and executing the PIP, Preparation of the PIP)

Requirements on paediatric drug formulations

Juvenile Animal Studies

Implications of the EU legislation for the pharmaceutical industry: perspectives, challenges and opportunities

Other regions, focus on US

The new legislation on the development and authorization of medicines for use in children aged 0 to 17 years was introduced in the European Union in January 2007. The Paediatric Regulation (Regulation/EC No 1901/2006 as amended) affects the regulatory environment for pharmaceutical companies and agencies enormously since it required many new tasks and responsibilities for the authorities, mainly the EMEA, and remarkable new requirements for the overall development plans of medicinal products for all types of pharmaceutical companies. Seminar 5 is designed to provide comprehensive information on the new European requirements for medicines for children, the legislation, regulatory bodies and procedures and their practical implementation in the daily work of a pharmaceutical company. In addition to the European requirements on the development of medicines in children the regulations of the FDA and of other regions are dealt with in detail.

Pharmacovigilance, i.e. the standard of constant monitoring of the safety of medicinal products after authorisation, is an important obligation of the marketing authorisation holder (MAH) and authorities. It requires constant exchange between companies and health authorities.

The EU legislation requires MAHs to provide the competent authorities with a description of their pharmacovigilance, risk management and quality system. Collecting, monitoring, assessing and evaluating information from healthcare professionals and patients on the adverse effects of medicinal products is conducted to identify new information about hazards associated with medicinal products and preventing harm to patients. Periodic Safety Reports (PSURs/PBRERs) and Risk Management Plans need to be generated and communicated regularly.

Depending on the signals observed, the MAH may have to implement actions for risk mitigation, for example changes to the SmPC or even measures on the marketing authorisation such as suspension or restriction of authorised therapeutic indications. The product information has to be kept up-to-date and communicated to health care professionals, patients and consumers in an effective and timely manner.

Companies manufacturing, testing or distributing active ingredients or medicinal products, clinical centres conducting clinical trials and research organisations performing studies need to follow common standards of quality system requirements. The quality system is supervised by national inspectorates who increasingly co-operate globally. If the establishment inspected is found to be compliant with the relevant requirements a license is issued as an authorisation to manufacture, test or distribute the medicinal product or active ingredient.

With the introduction of ICH Q 8, 9 and 10 principles, and with the increasing global trade of active ingredients and products, quality systems become more and more important in ensuring their quality.

The primary purpose of a quality system is to ensure that adequate quality standards are used and maintained. The Good Manufacturing Practice (GMP) applies to the manufacture and control of active ingredients and final dose forms of pharmaceuticals and their clinical supply, the Good Laboratory Practice (GLP) to non-clinical investigations of new compounds, the Good Clinical Practice (GCP) to the conduct of clinical studies, the Good Distribution Practice (GDP) to the storage and distribution of medicinal products.

Special GMP considerations for biopharmaceuticals including advanced therapies

What is special for biopharmaceuticals

GMP for starting materials

GMP of blood products and blood components

Are biopharmaceuticals subject to counterfeits

15.00 – 15.30 Coffee break

15.30 - 16.30 continued

16.30 - 18.00 The Regulatory Affairs department at the interphase

Which role the Regulatory Affairs department has at the interface of GMP authorization of manufacture and testing, GLP compliance of pre-clinical testing and GCP compliance of clinical trials

How supervision works – when an inspection is required – who performs the inspections – which authorization documents are required and how they are maintained – when and how the documents are submitted to agencies for CTA and marketing authorization

18.00 End of Day 1

19.00 Get-together with food and wine

Day 2

09.00 - 10.30 Experience with inspections conducted by the different inspectorates from Europe, U.S. and Japan

How an inspection is performed

10.30 – 11.00 Coffee break

11.00 – 12.30 continued

12.30 – 13.30 Lunch

13.30 – 15.00 Surveillance of medicines through testing in the EU/Europe

OMCL Network

CAP testing program and Market Surveillance

Official Control Authority Batch Release (OCABR)

15.00 – 15.30 Coffee break

15.30 – 16.30 The principles of GLP

Recording, archiving, reporting investigations

Global Implementation and mutual recognition

The competent authorities

16.30 - 17.30 The principles of GDP (Ralf Hess, Parexel)

Maintenance of the level of quality throughout the distribution chain

The Rapid Alert System

Product defects

Recalls

17.30 End of Day 2

For Full Course students:

Introduction of Homework Seminar 7

Day 3

09.00 – 10.30 The principles of GCP

Introduction

o Why we have GCP

o Declaration of Helsinki

o The ICH GCP process

o Ethical and scientific principles in clinical trials to ensure protection of trial subjects and integrity of trial results

The responsibilities of sponsors, e.g.

o Quality Control and Quality Assurance (Monitoring and Auditing)

o The interface to service providers

o GCP information flow and reporting requirements

The responsibilities of investigators, e.g.

o How to delegate trial tasks within a team

o Protocol adherence

o Informed Consent Procedure

o Source Data and Case Report Forms (CRFs)

o GCP information flow and reporting requirements

Typical GCP Inspection Findings

10.30 - 11.00 Coffee break

11.00 - 12.30 continued

12.30 - 13.15 Lunch

13.15 - 14.30 continued

14.30 End of Seminar 7

For Full Course students:

14.30 - 14.45 Coffee Break

14.45 - 15.30 Questions & Answers – Group work as preparation for the exam

Regulatory strategy for the introduction of changes in the manufacturing process

Intellectual Property Rights

Health Technology Assessment

According to the records of the EMA, constantly 25% of newly developed medicinal products submitted to the centralised authorisation procedure in Europe fail. This high failure rate is remarkable taking into account all the efforts installed in Europe within the 15 years from the time the EMA had been inaugurated. Numerous incentives are in place to stimulate regular pre-submission interactions with agencies to discuss the compliance of development programs with regulatory principles. Regulatory guidelines for all areas of drug development are available describing the regulatory standards. In order to translate these efforts into higher success rates of marketing authorisations an essential component of the overall regulatory strategy is the establishment of regular cross-functional interactions between teams of drug discovery and development, pharmaceutical development, marketing. Regulatory affairs should play an important role in this process. Health technology assessment is another increasingly important aspect of drug development, which requires earlier consideration in development concepts in the future. The seminar addresses concepts and tools by which strategic bridging is established and conducted efficiently in practice throughout the life cycle of the medicinal product.

Knowledge of the subject matter is required to understand the science of the product under development, to facilitate the adoption of regulatory principles and to integrate teams involved and information gained in this process. Regulatory affairs is thus determined by its interdisciplinary character requiring individuals committed to processes which are deadline-determined. Scientific and administrative requirements need to be integrated into the development concept, gap analysis of data packages as compared to regulatory requirements are conducted, teams need to be integrated internally and the interphase between the company and health authorities needs to be handled appropriately. The conduct of an agency meeting is trained at this seminar. Particular capabilities in preparing regulatory documents are required since style and content are special due to the orientation along regulatory requirements. Project management skills, time line awareness, interaction and communication skills are essential. Strategic planning, the ability to anticipate problems, to analyse complex situations and to offer the optimal strategy to achieve a certain strategic goal in a timely manner become important as the career progresses. These skills are necessary to communicate adequately with partners internally and externally. Certain tools for daily work are presented and ways to exchange with colleagues are discussed.